4 5 c EUCOMED GHTF vs MEDDEV_ Jan 2013 final

Comparison GHTF/SG5/N5:2012 vs. MEDDEV 2.7/3:2010
CIE February 14th, 2013
MEDDEV 2.7/3:2010
GHTF/SGS/N5: 2012
• Provides interpretation of Annex 7 of Directive
90/385/EEC and Annex X of Directive 93/42/EEC
as amended by Directive 2007/47/EC
• Note 4: provides clarification on application date
• Note 5: SAE reporting continues until completion
of investigation even if CE mark is granted
2. Scope: Pre market clinical investigations
conducted with non CE marked devices or CE
marked devices used outside the intended use
covered by the CE marking
• Provides guidance of adverse event reporting
during pre-market clinical investigations
• No application date given
• Dual reporting (SAE and Vigilance) not called out
MEDDEV is more explicit on
adverse event reporting when
study grant CE marking before the
end of the study
2. Scope: Pre-market clinical investigations undertaken
by the manufacturer to obtain regulatory approval for
CE marking or pre-market investigation that require
authorization before initiation
GHTF definition refers to pre
initiation approval, while the
MeddeV scope refers to the MDD /
AIMD CE marking and related
intended use
Not specifically mentioned that Post-market studies
are excluded. Reference to a separate MEDDEV
(2.12/2:2012) document for PMCF studies follow
When the investigational device used in a clinical study
is approved in a particular jurisdiction the NCA of that
country shall apply the post market reporting
requirements per GHTF/SG2/N54 document
GHTF is more explicit
Certain countries however apply
requirements of MEDDEV also for
Post-market studies.
3. Definitions: From ISO/FDIS 14155 but not all are
used (blinding/masking not in MEDDEV)
4. Definitions : as per ISO14155:2011 but not all are
used (SADE not in GHTF)
No term Serious Health Threat but indicated in Note
11 in section 7.1 “Reporting Timelines” refers to
events with potential Public Health Hazard as
reportable. However, Public Health Hazard is not
Serious Health Threat definition: any event type which
results in imminent risk to the study population of
death, serious injury or serious illness that requires
prompt remedial action. Reportable within 48 hours
following the determination that the Serious Health
Threat exists.
SAE definition: 1 note (aligned with ISO 14155)
GHTF better aligned with ISO
14155:2011 but not all relevant ISO
definitions are used in both
No definition of Serious Health
Threat or Public Health Hazard in
MEDDEV 2.7/3 or ISO 14155:2011
SAE definition: note 2 on device deficiencies that
might have led to SAE (not according to ISO 14155)
GHTF better aligned with ISO
MEDDEV 2.7/3: 2010
GHTF/SGS/N5: 2012
USADE and Sponsor definition aligned with
ISO/FDIS 14155
USADE definition: 2nd note added to
include unanticipated procedure-related
Sponsor definition: 2nd note added on
who can be the sponsor
5. Reportable events: same as MEDDEV +
note added referring to events
representing a Serious Health Threat
Nothing about updates in relation to
already reported events
In the case where opinions on incidence or
classification or relatedness of AE differ
between sponsor and investigator both
opinions have to be reported.
Some clarification notes added to definitions in GHTF.
However, unanticipated procedure-related SAEs are not
necessarily device related
4.Reportable events: same as GHTF
Reporting of new finding/updates in relation
to already reported events is included
If the manufacturer has a different opinion
from the investigator for device and/or
procedure relationship, the manufacturer´s
opinion has to be documented (specified in
the header of the excel tabular format)
Reportable events occurring in third
countries have to be reported
5. Report by whom : Sponsor of the Clinical
6. To whom to report
All NCAs where investigation has been
authorized to start in Member State, at the
same time using summary tabulation
All reportable events must be reported to
all NCA’s responsible for the jurisdiction
where the clinical investigation is
conducted, according to applicable
requirements in each jurisdiction.
Events must be reported by the Sponsor
(in section 5)
6. To whom to report
All NCAs where investigation is conducted
per national regulations
Difficult to find the information in the MEDDEV (only in excel
tabular format attached to the document)
GHTF is better aligned with ISO 14155:2011: The sponsor is
responsible for the classification of AEs and on going safety
evaluation of the clinical investigation and shall
Review the investigator’s assessment of all AEs and
determine and document in writing their seriousness
and relationship to the investigational device ; in case
of disagreement between the sponsor and the principal
investigator(s) the sponsor shall communicate both
opinions to the concerned parties, as defined in c), d)
and e) below” (meaning EC, CA etc…).
Not clear in the GHTF whether events from third countries
have to be reported to Europe
MEDDEV and GHTF are aligned
MEDDEV is more explicit.
“at the same time” not mentioned in the GHTF.
Where it has been “authorized” in MEDDEV vs. “conducted”
MEDDEV 2.7/3: 2010
GHTF/SGS/N5: 2012
7. Reporting timelines:
7. Timing for reporting
From Sponsor to NCAs
- Within 2 calendar days for events
indicating imminent risk of death, serious
injury or illness and that require prompt
remedial action for patients, users or other
persons (potential public health hazard in
Note 11)
- All other reportable events : immediately
but not later than 7 calendar days after
awareness by sponsor
From Sponsor to NCAs
- Within 48 hours: SAEs creating serious health threat
- No later than 10 elapsed calendar days: USADEs, SAEs
other than unanticipated resulting in life
threatening/permanent impairment/ fetal implications
- No later than 30 elapsed calendar days: all other
reportable events (in-patient or prolongation of
hospitalization/ resulting in intervention to prevent life
threatening) and device deficiencies which may have
led to serious injury
• Not the same timelines for different
categories of reportable events – GHTF has
more differentiation.
• GHTF not aligned with EU directive (i.e. can
30 days be considered as “immediately” per
Annex X 2.3.5?)
From Investigators to Sponsor
Acceptable timely conditions but not later
than within 3 calendar days after the
occurrence of the event
From Investigators to Sponsor
GHTF document does not include a specific section on
time of reports from investigator to Sponsor.
MEDDEV refers to the date of occurrence
which may be different from the awareness of
the event by the investigator
8. Format / content of the report
- Cumulative tabular format to all NCAs
- 3 categories for device and procedure
8. Format / content of the report
- No format: Not clearly defined if tabular format or
individual reporting but very detailed information
required (initial and final report)
- 4 categories for device and procedure relatedness
No alignment between MEDDEV and GHTF
No special conditions requirements
Special conditions requirements included: Combination
devices, unblinded controlled studies , implantable
medical devices…
Reporting of events occurring with “comparator” only
required in case of unblinded controlled studies
(otherwise reporting per post market requirements)
More explicit in GHTF regarding special
Reporting of events occurring with
“comparator” is required for all studies
No diagram
Diagram defining AE reportability and timelines
SAEs for all devices including comparator in
MEDDEV 2.7/3. Nothing mentioned regarding
the reporting SAEs of comparator in ISO
14155:2011 (only collecting)

similar documents